Abstract
The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the nonassociated HLA-B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2-Lys), in both HLA-B*27:05 and HLA-B*27:09. Furthermore, a small fraction of HLA-B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2-Arg) or the less common glutamine (P2-Gln) located at this anchor position. Overall these data indicate that peptides with P2-Lys should be considered as real ligands of HLA-B*27 molecules and taken into account while looking for putative peptides implicated in the AS.
| Original language | English (US) |
|---|---|
| Journal | Proteomics |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- 27
- Ankylosing spondylitis
- HLA-B
- Human leukocyte antigen
- Immunopeptidome
- Peptidome
- Transgenic rats
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
Cite this
The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position. / Yair-Sabag, Shira; Tedeschi, Valentina; Vitulano, Carolina; Barnea, Eilon; Glaser, Fabian; Melamed Kadosh, Dganit; Taurog, Joel D.; Fiorillo, Maria Teresa; Sorrentino, Rosa; Admon, Arie.
In: Proteomics, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position
AU - Yair-Sabag, Shira
AU - Tedeschi, Valentina
AU - Vitulano, Carolina
AU - Barnea, Eilon
AU - Glaser, Fabian
AU - Melamed Kadosh, Dganit
AU - Taurog, Joel D.
AU - Fiorillo, Maria Teresa
AU - Sorrentino, Rosa
AU - Admon, Arie
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the nonassociated HLA-B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2-Lys), in both HLA-B*27:05 and HLA-B*27:09. Furthermore, a small fraction of HLA-B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2-Arg) or the less common glutamine (P2-Gln) located at this anchor position. Overall these data indicate that peptides with P2-Lys should be considered as real ligands of HLA-B*27 molecules and taken into account while looking for putative peptides implicated in the AS.
AB - The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the nonassociated HLA-B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2-Lys), in both HLA-B*27:05 and HLA-B*27:09. Furthermore, a small fraction of HLA-B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2-Arg) or the less common glutamine (P2-Gln) located at this anchor position. Overall these data indicate that peptides with P2-Lys should be considered as real ligands of HLA-B*27 molecules and taken into account while looking for putative peptides implicated in the AS.
KW - 27
KW - Ankylosing spondylitis
KW - HLA-B
KW - Human leukocyte antigen
KW - Immunopeptidome
KW - Peptidome
KW - Transgenic rats
UR - http://www.scopus.com/inward/record.url?scp=85043597768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043597768&partnerID=8YFLogxK
U2 - 10.1002/pmic.201700249
DO - 10.1002/pmic.201700249
M3 - Article
C2 - 29393594
AN - SCOPUS:85043597768
JO - Proteomics
JF - Proteomics
SN - 1615-9853
ER -